Soluble exoantigens of Trypanosoma lewisi were obtained from short-culture systems of dividing epimastigotes and non-dividing trypomastigotes incubated in phosphate-buffered saline glucose solution (PBSG) for 3 h at 37 degrees C. Suppression of normal rat-spleen cell responses to mitogen concanavalin A (Con A) occurred at high exoantigens concentrations. The epimastigote-derived exoantigens were more suppressive than the trypomastigote-derived exoantigens. The suppression of Con A stimulation was ablated by the addition of exogenous interleukin-2 (IL-2) or washing of spleen cells that had been incubated with suppressing concentrations of the epimastigote exoantigens for 24 h prior to Con A stimulation. These results strongly suggest that exoantigens of T. lewisi play an important immunoregulatory role during the course of infection and that they achieve this by inhibiting the production of IL-2 by T-helper cells.
Infections by Trypanosoma lewisi are characterized by hyporesponsiveness of the immune system during the early phase of parasitaemia. Blastogenic response of normal rat spleen cells to amphiphilic and hydrophilic components of Triton X-114 solubilized epimastigote forms of T. lewisi which characterizes the early phase of infection showed that suppression of responses to mitogens Concanavalin A (Con-A) and lipopolysaccharide (LPS) occurred exclusively with the amphiphilic fraction that consists of integral surface membrane constituents. The Con-A-induced suppression by the amphiphilic constituents was ablated by addition of exogenous IL-2 or by the removal of the adherent cell population in the cultures. This suggests that the integral surface membrane components play an important regulatory role in infections with Trypanosoma lewisi, through complex mechanisms that probably involve the B cells and suppressor macrophages; the suppressor macrophages probably produce a suppressor factor that inhibits the proliferation of T helper cells and subsequently the production of interleukin-2.
In rats infected with Trypanosoma lewisi, parasitaemia normally resolves by day 32; thereafter, the rodents become solidly immune to re-infection. Rats treated on day 5 of infection with a single i.m. dose of 35 mg/kg of the trypanocidal drug ethidium bromide (EB) had recovered from parasitaemia by day 12, whereas berenil (BE) given at 100 mg/kg, more than twice the recommended dose, had no effect on parasitaemia. However, rats treated for 4 consecutive days beginning on day 5 of infection with Lampit (LA) and Radanil (RA) at 350 mg/kg showed no parasitaemia on days 16 and 20, respectively. EB was the most effective drug in lowering the total IgG antibody as compared with the control animals, whose specific IgG titres remained elevated for over 200 days after the parasitaemia had been cleared. LA also significantly reduced the antibody levels through day 240, whereas RA only transitorily depressed the antibody levels on days 20 and 30. BE, which had no effect on parasitaemia, correspondingly failed to depress the total IgG levels. Re-challenge infection of the drug-treated, recovered animals on day 240 (208 days after the normal resolution of the infection) revealed that except for the EB group, which displayed transitory parasitaemia for 4 days, other treated and control rats completely resisted the challenge; pre-challenge antibody titres were lower than 1:160 in EB-treated animals in contrast to the levels of 1:320 or higher measured in the other drug-treated and control animals, which resisted the infection.(ABSTRACT TRUNCATED AT 250 WORDS)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.